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Title: Hyperglycemia and anthocyanin inhibit quercetin metabolism in HepG2 cells

item HASHIMOTO, NAOTO - National Agricultural Research Center For Kyushu Okinawa Region
item BLUMBERG, JEFFREY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item CHEN, CHUNG-YEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Medicinal Food
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/2015
Publication Date: 2/1/2016
Citation: Hashimoto, N., Blumberg, J.B., Chen, C. 2016. Hyperglycemia and anthocyanin inhibit quercetin metabolism in HepG2 cells. Journal of Medicinal Food. 19(2):141-147.

Interpretive Summary: Polyphenols are prevalent in fruits, vegetables, whole grains, and spices. Their consumptions have been linked to reduced risk for chronic diseases, such as heart disease and cancers, via actions to clean up free radicals and reduce inflammation. However, the efficacy of these health benefits is dependent on how they are absorbed in the gut and are transformed in the small intestine and liver. The transformation of polyphenols has been appreciated to decrease the extent of health benefits of consumed polyphenols. There are certain conditions in the body in which the rate of the transformation of absorbed polyphenols is accelerated. For example, a high blood glucose level, which is a hallmark condition in people with glucose intolerance and diabetes, may be associated with increased polyphenol transformations in the liver and small intestine. Thus, we examined whether a high glucose condition mimicking the high blood glucose condition found in people with diabetes would increase the transformation of quercetin, a polyphenol commonly found in apples and tea, in cultured liver cells. We found that the high blood glucose condition decreased the transformation of quercetin in the cultured liver cells. Future human studies are warranted to demonstrate whether polyphenols will not be extensively transformed in people with the diabetes.

Technical Abstract: A high glucose (Glu) milieu promotes generation of reactive oxygen species, which may not only cause cellular damage, but also modulate phase II enzymes that are responsible for the metabolism of flavonoids. Thus, we examined the effect of a high Glu milieu on quercetin (Q) metabolism in HepG2 cells. HepG2 cells were grown for 3 days in Glu ranging from 5.5 to 50 mmol/L and/or cyanidin-3-glucoside (C3G) ranging from 0 to 25 micro-mol/L. Subsequently, the capacity of HepG2 cells to metabolize Q was assessed for up to 16 h. Q metabolites were analyzed by high-performance liquid chromatography. Four major Q metabolites were observed in the culture medium and inside the HepG2 cells. Three of these metabolites appear to be sulfated forms of Q or methylated Q, and one was a methylated Q. These metabolites and Q itself were reduced or tended to be reduced in cells grown in a high Glu compared to a normal Glu medium. Addition of C3G or superoxide dismutase plus catalase did not prevent or enhance reduction of Q metabolites. In vitro, a hyperglycemic milieu decreases the production of the principal Q metabolites in HepG2 cells, mediated through mechanisms independent of oxidative stress.